The objective of the proposed research is to quantitate the influences of factors which may modify susceptibility to oxygen toxicity in patients with pulmonary or respiratory insufficiency. Effects and interactions which will be studied include those of veno-arterial shunting to reduce arterial PO2, acute and chronic hypercapnia, and chronic hypoxia with and without chronic hypercapnia. Survival times in large numbers of rats will be used to study these effects at oxygen pressures of 1.0, 1.5, 2.0, 2.8, and 3.5 ata. Over this range of oxygen pressures we will study effects on pulmonary oxygen poisoning, with an increasing degree of neuroendocrine interaction in the absence of convulsions at the lower pressures and in their presence at higher pressures. Analysis and description of the effects will be aided by an experimental design which facilitates employment of previously used probability-log transformations of data to define susceptibility to oxygen toxicity at a single pressure and log-log transformations to define relative effects at different oxygen pressures. When analysis of systematic oxygen exposures of intact rats have identified conditions which have prominent effects on susceptibility to oxygen poisoning, studies designed to find biochemical correlates of these effects will be carried out. To obtain data that is quantitatively relevant to man, it will ultimately be necessary to study very selectively in man those factors which are found to have the greatest potential for altering susceptibility to oxygen poisoning. The results of the proposed rat studies will provide the basis for an effective and practical design of such experiments.